Combinatorial chemistry is a drug discovery technology being employed by pharmaceutical companies worldwide. Through combinatorial chemistry, a strategy of diversity is used to synthesize as many different molecules as possible and test their reaction to a specific xe2x80x9ctargetxe2x80x9d, such as a disease or cell structure. Screening is the chemical assay of the molecules with the xe2x80x9ctargetxe2x80x9d. If any of the molecule(s) show some reaction to the xe2x80x9ctargetxe2x80x9d during screening, the molecule(s) become a candidate for a commercial drug. The candidate molecule(s) are then characterized to determine both their composition and structure to enable additional synthesis and testing One technique of employing combinatorial chemistry utilizes polystyrene beads as a support structure for the molecules to be tested,
The polystyrene beads are small, having diameters ranging from 1000 microns to less than 20 microns. Large numbers of polystyrene beads coated with members of a single class of compound, such as peptides, constitute a collection known as a library. Each library can include thousands of the beads with different molecules, yet each bead contains only a single type of molecule. Processing of the beads to test their reaction to specific xe2x80x9ctargetxe2x80x9d requires exposure to a bio reagent indicative of the xe2x80x9ctargetxe2x80x9d. Each bead is screened to determine if there is any activity between the molecule(s) on the bead and the xe2x80x9ctargetxe2x80x9d. Any activity between the molecule on a bead and the xe2x80x9ctargetxe2x80x9d is considered a xe2x80x9chitxe2x80x9d and that molecule is further tested.
The usefulness of the bead technique is limited by the difficulty of manipulating individual beads, screening the molecules and then characterizing the xe2x80x9chitsxe2x80x9d. Presently, a technique of electrospray mass spectrometry is utilized for characterizing the xe2x80x9chitsxe2x80x9d, in which the characterization process can lake as long as 15 minutes to complete. Because the screening of a large library may result in the discovery of many thousands of possible xe2x80x9chitsxe2x80x9d, the characterization of large libraries requires huge expenditures of time and labor. This has necessitated the use of smaller libraries, which do not take fill advantage of the combinatorial chemistry benefits.
Work by investigators has shown that beads can be characterized much more rapidly using Time-of-Flight/Secondary Ion Mass Spectrometry (TOF/SIMS). TOF/SIMS is another mass spectrometer technique. The TOF/SIMS reduces the time required for characterization of a single bead from 15 minutes to less than 1 seconds. However, the manual labor required to array the beads on a substrate after the screening process has been performed and also keep the beads positioned during the TOF/SIMS characterization has limited the usefulness of this technique.
It is an object of the present invention to provide a system and method to screen molecules on a library of beads, while also characterizing the molecules on the beads.
It is an object of the present invention to reduce the time it takes to screen and characterized molecules on a library of beads.
It is an object of the present invention to provide a bead holder to aid in the above-mentioned objects of the present invention.
The present invention is a combinatorial chemistry system and method of use for the dual processing of different molecules coated on a library of beads. The system includes beads coated with different molecules on each bead, a bead holder, screening equipment and characterization equipment. The bead holder retains the beads so that each of the beads has an exposed first section of the bead which is exposed independently of an exposed second section of the bead. The screening equipment and characterization equipment is used to assay and characterize the molecules on each bead. The method of use includes screening the exposed first section of the beads which are coated with molecules and characterizing the molecules located on the exposed second section of the beads. The method utilizes a library of the beads in the bead holder, whereby the bead holder retains the beads as described above. Included in the method is the screening of molecules on the beads, while allowing the characterization of the molecules on beads during the screening process.